Nano Tweezers Take Molecules from Cells without Destroying Them

Scientists have created nano tweezers that extract single molecules from cells without destroying them. The device should help researchers study the inner workings of cells in real-time.

by Lina Zeldovich

January 25, 2019

A team of scientists at the Imperial College London developed a tiny tool that lets them extract single molecules from cells without destroying them. Named electric nano tweezers, the instrument uses a powerful electric field to pluck the DNA and other particles from living cells, letting researchers study their inner workings in real time.

Biologists strive to understand the cell’s spatial organization and the molecular dynamics within them. Mapping the molecular diversity of the seemingly identical cells can help medics build more precise models of disease and create patient-specific therapies. But the traditional methods of studying what happens inside a cell usually involves bursting it, which kills the cell and muddles the information it can provide. Scientists can obtain a simple “snapshot” of the cells’ profile at a particular point in time, but lose the cells’ spatial and dynamic information and how it changes over time.

Having the ability to analyze this in real time would allow scientists to build a “human cell atlas” and understand how healthy cells work and what goes awry when they malfunction. “It is a different approach to single cell analysis,” said Binoy Paulose Nadappuram, an author of the study.

To provide researchers with this ability, Nadappuram, together with Paolo Cadinu and other colleagues at the Imperial College London, created electric nano tweezers. The tweezers are built from a sharp glass rod that has a pair of tiny electrodes, made from a graphite-like compound forged by a pyrolysis of butane, at the end. In the presence of oxygen, the carbon-containing butane would burn, generating carbon dioxide and water. However, when heated without oxygen, the carbon remains solid and forms the tweezers’ electrodes. The electrodes have a 10- to 20-nanometre gap between them. When an alternating current voltage is applied, the small gap creates a highly localized powerful electrical field that traps the molecules and other particles inside cells.

Using their new tool, researchers demonstrated that they were able to manipulate and extract several different items from various regions of the cell, including mitochondria from the cell body, RNA from different locations in the cytoplasm, and DNA from the nucleus. The ability to study the mitochondria, the cells’ powerhouse that breaks down nutrients and creates energy, is of particular interest to scientists. The mitochondria is said to have its own genome, which differs from the cells’ DNA. Those genetic variations have been implicated in health and disease.

The tweezers can also be used to insert particles into cells, such as a piece of microRNA, to investigate its gene expression pattern and role in disease development. Inserting microRNAs can alter the functioning of the cell and lead to novel therapies. The ability to regulate the functioning of individual cells at that level is an important concept in precision and personalized medicine.

The tweezers can be used for cell biopsies and to move molecules between cells.

“You can move a specific molecule from one environment to other, at nanometer scale,” Nadappuram said. “You can also imagine using it for building synthetic cells where you assemble them from various building blocks.”

Professor Ratnasingham Sooryakumar at the Ohio State University’s Department of Physics, who had worked on magnetic tweezers and cell manipulation, finds the new tool very exciting. “It’s a very interesting, clever application,” he said. “And they applied it to biological systems and proved that it’s a very viable technique.”

Sooryakumar thinks the new tool has many potential applications that could be further explored. Echoing the study authors’ ideas, he also suggests to try inserting some materials or molecules into the cells and study the outcome. “It would be interesting to do the reverse. Take some genetic material and introduce it into a specific part of the cells and see how the cells respond,” he said.

These manipulations can open doors to novel cell therapies that can be tried and tested in real time, while researchers watch the cells’ reactions.

“You can treat cells and see how they are responding and do timely analysis,” Sooryakumar said, of the many uses the team’s creation may have. “They opened up opportunities for all kinds of things.”